Variant X-3015059-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001011719.2(ARSH):c.430C>A(p.Pro144Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00713 in 1,208,826 control chromosomes in the GnomAD database, including 40 homozygotes. There are 2,791 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., 209 hem., cov: 22)

Exomes 𝑓: 0.0073 ( 34 hom. 2582 hem. )

Consequence

ARSH
NM_001011719.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.54

Variant links:

Genes affected

ARSH (HGNC:32488): (arylsulfatase family member H) Sulfatases, such as ARSH, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ARSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011798948).

BP6

Variant X-3015059-C-A is Benign according to our data. Variant chrX-3015059-C-A is described in ClinVar as [Benign]. Clinvar id is 713928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-3015059-C-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSH	NM_001011719.2 linkuse as main transcript	c.430C>A	p.Pro144Thr	missense_variant	4/9	ENST00000381130.3	NP_001011719.1	Q5FYA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSH	ENST00000381130.3 linkuse as main transcript	c.430C>A	p.Pro144Thr	missense_variant	4/9	1	NM_001011719.2	ENSP00000370522.3		Q5FYA8

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

620

AN:

111107

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

209

AN XY:

33307

show subpopulations

Gnomad AFR

AF:

0.000851

Gnomad AMI

AF:

0.0869

Gnomad AMR

AF:

0.000964

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.000771

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00655

Gnomad OTH

AF:

0.00200

GnomAD3 exomes

AF:

0.00649

AC:

1181

AN:

182092

Hom.:

AF XY:

0.00665

AC XY:

443

AN XY:

66612

show subpopulations

Gnomad AFR exome

AF:

0.000916

Gnomad AMR exome

AF:

0.000476

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.0287

Gnomad NFE exome

AF:

0.00774

Gnomad OTH exome

AF:

0.00731

GnomAD4 exome

AF:

0.00729

AC:

8003

AN:

1097666

Hom.:

Cov.:

AF XY:

0.00711

AC XY:

2582

AN XY:

363034

show subpopulations

Gnomad4 AFR exome

AF:

0.000644

Gnomad4 AMR exome

AF:

0.000682

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.00774

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.00558

AC:

620

AN:

111160

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

209

AN XY:

33370

show subpopulations

Gnomad4 AFR

AF:

0.000849

Gnomad4 AMR

AF:

0.000963

Gnomad4 ASJ

AF:

0.00265

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.000774

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.00655

Gnomad4 OTH

AF:

0.00198

Alfa

AF:

0.00561

Hom.:

260

Bravo

AF:

0.00381

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00658

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00684

AC:

ExAC

AF:

0.00649

AC:

788

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.012

MetaSVM

Uncertain

0.72

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.62

Sift

Benign

0.072

Sift4G

Benign

0.068

Polyphen

0.83

Vest4

0.28

MVP

0.56

MPC

0.61

ClinPred

0.10

GERP RS

3.9

Varity_R

0.47

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over